PDF(Pubmed)
Abstract：
Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.
摘要：
急性髓细胞性白血病（AML）是一种与衰老相关的异质性造血系统恶性肿瘤。在这项研究中,共纳入1,474例新诊断的AML患者的RNA测序数据，94%的病例获得了靶向或全外显子组测序数据。衰老相关因素包括年龄和克隆造血（CH）的相关性，性别,和基因组/转录组概况(基因融合，基因突变,和基因表达网络或途径)进行了系统分析。总的来说,60岁及以上的AML患者预后明显不佳。随着年龄的增长，世界卫生组织分类中定义的基因融合频率降低，而基因突变的阳性率,尤其是与CH相关的，增加。此外,基因融合阴性(GF-)患者的基因突变数量高于GF患者.基于CH和骨髓增生异常综合征（MDS）相关突变的状态，在GF-AML队列中确定了三个突变亚组，即,CH-AML,CH-MDS-AML,和其他GFAML。值得注意的是,CH-MDS-AML在老年和男性病例中占主导地位，血细胞减少,和显著不良的临床结果。此外,基因表达网络，包括HOXA/B，血小板因子，炎症反应是AML患者与衰老和预后不良相关的最显著特征.因此，我们的工作揭示了不同年龄之间相互作用的复杂调节电路，性别,和AML的分子群。
